EWAS
As
DMP_As_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'As_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 11440
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 19530
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.065045
# Number of DMRs identified: 1
# rm(DMP_As_cord); gc()
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$As_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.1888243
TestCDFs2(Z = Z, y = y, X = X)
# 0.4438389
# rm(DMP_As_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
12
|
9217389
|
9217859
|
0
|
470
|
0
|
0
|
9
|
No adjustment for fish consumption
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As/As_log2_manhattan_DMP_adj.png")

As, female
pDatcordMetal_F = pDatcordMetal[pDatcordMetal$female_d == 1,]
pDatcordMetal_F$race_child2 = as.factor(as.numeric(pDatcordMetal_F$race_child2))
DMP_As_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'As_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 17949
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 16668
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.9807579
# Number of DMRs identified: 2
# Global DNAm
ComBat.Betas.Metals_F = ComBat.Betas.Metals[,colnames(ComBat.Betas.Metals) %in% rownames(pDatcordMetal_F)]
ComBat.Betas.Metals_F = ComBat.Betas.Metals_F[,match(rownames(pDatcordMetal_F), colnames(ComBat.Betas.Metals_F))]
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$As_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.2559703
TestCDFs2(Z = Z, y = y, X = X)
# 0.6246159
# rm(DMP_As_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
3
|
186490655
|
186490915
|
0
|
260
|
0
|
1.8e-06
|
5
|
|
11
|
34460106
|
34460386
|
0
|
280
|
0
|
4.7e-06
|
7
|
No adjustment for fish consumption
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_F/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_F/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_F/As_log2_manhattan_DMP_adj.png")

As, male
pDatcordMetal_M = pDatcordMetal[pDatcordMetal$female_d == 0,]
pDatcordMetal_M$race_child2 = as.factor(as.numeric(pDatcordMetal_M$race_child2))
DMP_As_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'As_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 12218
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 17743
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.011027
# Number of DMRs identified: 6
# Global DNAm
ComBat.Betas.Metals_M = ComBat.Betas.Metals[,colnames(ComBat.Betas.Metals) %in% rownames(pDatcordMetal_M)]
ComBat.Betas.Metals_M = ComBat.Betas.Metals_M[,match(rownames(pDatcordMetal_M), colnames(ComBat.Betas.Metals_M))]
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$As_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.5073422
TestCDFs2(Z = Z, y = y, X = X)
# 0.4807815
# rm(DMP_As_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
12
|
9217389
|
9217859
|
0.0000000
|
470
|
0.0000000
|
0.0000000
|
9
|
|
20
|
3051953
|
3052345
|
0.0000000
|
392
|
0.0000000
|
0.0000001
|
9
|
|
11
|
18433499
|
18433683
|
0.0000000
|
184
|
0.0000001
|
0.0000770
|
4
|
|
11
|
2890628
|
2890670
|
0.0000178
|
42
|
0.0000214
|
0.1539887
|
6
|
|
11
|
1036676
|
1036766
|
0.0000179
|
90
|
0.0000214
|
0.0753032
|
3
|
|
6
|
32063990
|
32064032
|
0.0060759
|
42
|
0.0060759
|
1.0000000
|
2
|
No adjustment for fish consumption
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_M/As_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_M/As_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/As_M/As_log2_manhattan_DMP_adj.png")

Ba
DMP_Ba_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Ba_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 21408
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 18967
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.006289
# Number of identified DMR: 0
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Ba_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.9650461
# rm(DMP_Ba_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba/Ba_log2_manhattan_DMP_adj.png")

Ba, female
DMP_Ba_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Ba_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 16994
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 13428
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.7990795
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Ba_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.864574
TestCDFs2(Z = Z, y = y, X = X)
# 0.9088558
# rm(DMP_Ba_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
10
|
135051255
|
135051581
|
0
|
326
|
0
|
2e-06
|
7
|
|
8
|
144635259
|
144635610
|
0
|
351
|
0
|
5e-06
|
9
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_F/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_F/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_F/Ba_log2_manhattan_DMP_adj.png")

Ba, male
DMP_Ba_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Ba_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 16173
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 14282
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.865515
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Ba_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.6927273
TestCDFs2(Z = Z, y = y, X = X)
# 0.8277251
# rm(DMP_Ba_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
4
|
169239618
|
169240010
|
0
|
392
|
0
|
0e+00
|
7
|
|
10
|
135278716
|
135279147
|
0
|
431
|
0
|
2e-07
|
5
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_M/Ba_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_M/Ba_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Ba_M/Ba_log2_manhattan_DMP_adj.png")

Cd
DMP_Cd_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Cd_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 13284
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 16155
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.9008795
# Number of DMRs identified: 5
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Cd_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.9348243
# rm(DMP_Cd_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
3
|
156323951
|
156324118
|
0.0000000
|
167
|
0.0000000
|
0.0000030
|
3
|
|
13
|
110319561
|
110319607
|
0.0000000
|
46
|
0.0000000
|
0.0000233
|
3
|
|
17
|
46685291
|
46685448
|
0.0000000
|
157
|
0.0000000
|
0.0000207
|
5
|
|
2
|
200468625
|
200468832
|
0.0000001
|
207
|
0.0000001
|
0.0001106
|
3
|
|
6
|
30039141
|
30039175
|
0.0095070
|
34
|
0.0095070
|
1.0000000
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd/Cd_log2_manhattan_DMP_adj.png")

Cd, female
DMP_Cd_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Cd_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 19177
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 18135
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.9732893
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Cd_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.6678424
TestCDFs2(Z = Z, y = y, X = X)
# 0.7811745
# rm(DMP_Cd_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
7
|
27225810
|
27225897
|
2.0e-07
|
87
|
4.0e-07
|
0.0009656
|
4
|
|
2
|
200468625
|
200468728
|
4.5e-06
|
103
|
4.5e-06
|
0.0171663
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_F/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_F/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_F/Cd_log2_manhattan_DMP_adj.png")

Cd, male
DMP_Cd_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Cd_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 8842
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 15768
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.9683207
# Number of DMRs identified: 1
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Cd_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.4173395
# rm(DMP_Cd_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
19
|
37742738
|
37742956
|
0
|
218
|
0
|
1e-07
|
4
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_M/Cd_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_M/Cd_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cd_M/Cd_log2_manhattan_DMP_adj.png")

Cr
DMP_Cr_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Cr_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 19469
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 19356
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.9710716
# Number of DMRs identified: 5
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Cr_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.8160506
TestCDFs2(Z = Z, y = y, X = X)
# 0.8524831
# rm(DMP_Cr_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
8
|
13373032
|
13373141
|
0.0e+00
|
109
|
0.0e+00
|
0.0000063
|
3
|
|
6
|
33245700
|
33246008
|
0.0e+00
|
308
|
0.0e+00
|
0.0000023
|
13
|
|
10
|
114713023
|
114713187
|
0.0e+00
|
164
|
0.0e+00
|
0.0000259
|
3
|
|
17
|
46681110
|
46681401
|
0.0e+00
|
291
|
1.0e-07
|
0.0000623
|
6
|
|
17
|
46641862
|
46642011
|
8.8e-05
|
149
|
8.8e-05
|
0.2079115
|
2
|
No adjustment for fish consumption
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr/Cr_log2_manhattan_DMP_adj.png")

Cr, female
DMP_Cr_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Cr_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 15600
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 13645
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.8363976
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Cr_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.9279794
# rm(DMP_Cr_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
8
|
13373032
|
13373141
|
0e+00
|
109
|
0e+00
|
0.0000145
|
3
|
|
6
|
31148369
|
31148666
|
1e-07
|
297
|
1e-07
|
0.0001264
|
12
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_F/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_F/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_F/Cr_log2_manhattan_DMP_adj.png")

Cr, male
DMP_Cr_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Cr_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 13268
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 15910
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.909677
# Number of identified DMR: 0
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Cr_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.5576744
TestCDFs2(Z = Z, y = y, X = X)
# 0.7528378
rm(DMP_Cr_M_cord); gc()
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_M/Cr_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_M/Cr_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cr_M/Cr_log2_manhattan_DMP_adj.png")

Cs
DMP_Cs_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Cs_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 28868
# Unadjusted, FDR<0.05: 5
# Unadjusted, pBonf<0.05: 3
# Adjusted, N = 361
# Adjusted, p<0.05: 19239
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.018459
# Number of DMRs identified: 18
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Cs_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.5068162
TestCDFs2(Z = Z, y = y, X = X)
# 0.5042182
# rm(DMP_Cs_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
4
|
174421376
|
174422626
|
0.0000000
|
1250
|
0.0000000
|
0.0000000
|
7
|
|
6
|
33280051
|
33280478
|
0.0000000
|
427
|
0.0000000
|
0.0000000
|
14
|
|
6
|
28601268
|
28601519
|
0.0000000
|
251
|
0.0000000
|
0.0000001
|
11
|
|
6
|
32847440
|
32847845
|
0.0000000
|
405
|
0.0000000
|
0.0000003
|
17
|
|
6
|
30881315
|
30881842
|
0.0000000
|
527
|
0.0000000
|
0.0000002
|
21
|
|
17
|
17603530
|
17603837
|
0.0000000
|
307
|
0.0000000
|
0.0000008
|
4
|
|
20
|
57427411
|
57427762
|
0.0000000
|
351
|
0.0000000
|
0.0000016
|
15
|
|
1
|
75590911
|
75591029
|
0.0000000
|
118
|
0.0000000
|
0.0000167
|
3
|
|
12
|
44152508
|
44152940
|
0.0000000
|
432
|
0.0000000
|
0.0000091
|
11
|
|
12
|
1025528
|
1025755
|
0.0000001
|
227
|
0.0000001
|
0.0000898
|
3
|
|
12
|
54763210
|
54763433
|
0.0000001
|
223
|
0.0000001
|
0.0000934
|
3
|
|
19
|
10736005
|
10736117
|
0.0000001
|
112
|
0.0000001
|
0.0002107
|
5
|
|
3
|
141087186
|
141087363
|
0.0000001
|
177
|
0.0000001
|
0.0001661
|
5
|
|
8
|
43131259
|
43131656
|
0.0000001
|
397
|
0.0000001
|
0.0000851
|
5
|
|
15
|
69325270
|
69325560
|
0.0000001
|
290
|
0.0000001
|
0.0001177
|
5
|
|
5
|
78985424
|
78985592
|
0.0000002
|
168
|
0.0000002
|
0.0003553
|
9
|
|
17
|
46388389
|
46388465
|
0.0000002
|
76
|
0.0000003
|
0.0012942
|
3
|
|
6
|
31651019
|
31651029
|
0.0061778
|
10
|
0.0061778
|
1.0000000
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs/Cs_log2_manhattan_DMP_adj.png")

Cs, female
DMP_Cs_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Cs_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 14228
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 11077
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.7878935
# Number of DMRs identified: 4
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Cs_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.683642
TestCDFs2(Z = Z, y = y, X = X)
# 0.9583828
# rm(DMP_Cs_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
12
|
44152508
|
44152940
|
0.00e+00
|
432
|
0.00e+00
|
0.0000000
|
11
|
|
6
|
117923794
|
117924070
|
0.00e+00
|
276
|
0.00e+00
|
0.0000220
|
8
|
|
1
|
26233331
|
26233623
|
0.00e+00
|
292
|
1.00e-07
|
0.0000511
|
10
|
|
6
|
32847761
|
32847830
|
1.61e-05
|
69
|
1.61e-05
|
0.0879654
|
5
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_F/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_F/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_F/Cs_log2_manhattan_DMP_adj.png")

Cs, male
DMP_Cs_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Cs_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 23725
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 21075
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.092447
# Number of DMRs identified: 14
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Cs_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.9380089
TestCDFs2(Z = Z, y = y, X = X)
# 0.5680556
# rm(DMP_Cs_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
6
|
31650734
|
31651362
|
0e+00
|
628
|
0e+00
|
0.0000000
|
21
|
|
8
|
43131259
|
43132507
|
0e+00
|
1248
|
0e+00
|
0.0000000
|
8
|
|
15
|
69325270
|
69325560
|
0e+00
|
290
|
0e+00
|
0.0000000
|
5
|
|
17
|
17603530
|
17604146
|
0e+00
|
616
|
0e+00
|
0.0000000
|
5
|
|
12
|
108634146
|
108634275
|
0e+00
|
129
|
0e+00
|
0.0000017
|
3
|
|
6
|
28601268
|
28601519
|
0e+00
|
251
|
0e+00
|
0.0000024
|
11
|
|
3
|
141087186
|
141087363
|
0e+00
|
177
|
0e+00
|
0.0000098
|
5
|
|
10
|
134150488
|
134150760
|
0e+00
|
272
|
1e-07
|
0.0000454
|
7
|
|
6
|
30881463
|
30881766
|
1e-07
|
303
|
1e-07
|
0.0001063
|
15
|
|
19
|
51774376
|
51774666
|
1e-07
|
290
|
1e-07
|
0.0001355
|
4
|
|
14
|
21148813
|
21148957
|
1e-07
|
144
|
1e-07
|
0.0003044
|
2
|
|
6
|
28446839
|
28447115
|
1e-07
|
276
|
2e-07
|
0.0002057
|
4
|
|
4
|
187422004
|
187422119
|
2e-07
|
115
|
2e-07
|
0.0006142
|
5
|
|
13
|
23309929
|
23310203
|
4e-07
|
274
|
4e-07
|
0.0005223
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_M/Cs_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_M/Cs_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cs_M/Cs_log2_manhattan_DMP_adj.png")

Cu
DMP_Cu_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Cu_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 31830
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 57348
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.845378
# Number of DMRs identified: 4
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Cu_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.3984576
TestCDFs2(Z = Z, y = y, X = X)
# 0.05580438
# rm(DMP_Cu_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
4
|
174421376
|
174422626
|
0.0000000
|
1250
|
0.0000000
|
0.0000000
|
7
|
|
6
|
33280051
|
33280478
|
0.0000000
|
427
|
0.0000000
|
0.0000000
|
14
|
|
6
|
28601268
|
28601519
|
0.0000000
|
251
|
0.0000000
|
0.0000001
|
11
|
|
6
|
32847440
|
32847845
|
0.0000000
|
405
|
0.0000000
|
0.0000003
|
17
|
|
6
|
30881315
|
30881842
|
0.0000000
|
527
|
0.0000000
|
0.0000002
|
21
|
|
17
|
17603530
|
17603837
|
0.0000000
|
307
|
0.0000000
|
0.0000008
|
4
|
|
20
|
57427411
|
57427762
|
0.0000000
|
351
|
0.0000000
|
0.0000016
|
15
|
|
1
|
75590911
|
75591029
|
0.0000000
|
118
|
0.0000000
|
0.0000167
|
3
|
|
12
|
44152508
|
44152940
|
0.0000000
|
432
|
0.0000000
|
0.0000091
|
11
|
|
12
|
1025528
|
1025755
|
0.0000001
|
227
|
0.0000001
|
0.0000898
|
3
|
|
12
|
54763210
|
54763433
|
0.0000001
|
223
|
0.0000001
|
0.0000934
|
3
|
|
19
|
10736005
|
10736117
|
0.0000001
|
112
|
0.0000001
|
0.0002107
|
5
|
|
3
|
141087186
|
141087363
|
0.0000001
|
177
|
0.0000001
|
0.0001661
|
5
|
|
8
|
43131259
|
43131656
|
0.0000001
|
397
|
0.0000001
|
0.0000851
|
5
|
|
15
|
69325270
|
69325560
|
0.0000001
|
290
|
0.0000001
|
0.0001177
|
5
|
|
5
|
78985424
|
78985592
|
0.0000002
|
168
|
0.0000002
|
0.0003553
|
9
|
|
17
|
46388389
|
46388465
|
0.0000002
|
76
|
0.0000003
|
0.0012942
|
3
|
|
6
|
31651019
|
31651029
|
0.0061778
|
10
|
0.0061778
|
1.0000000
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu/Cu_log2_manhattan_DMP_adj.png")

Cu, female
DMP_Cu_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Cu_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 34435
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 17137
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.061581
# Number of DMRs identified: 3
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Cu_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.2253006
TestCDFs2(Z = Z, y = y, X = X)
# 0.2135721
# rm(DMP_Cu_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
20
|
57427442
|
57427830
|
0.0000000
|
388
|
0.0000000
|
0.0000017
|
15
|
|
7
|
1250087
|
1250182
|
0.0000576
|
95
|
0.0000864
|
0.2126146
|
3
|
|
11
|
368637
|
368712
|
0.0067564
|
75
|
0.0067564
|
1.0000000
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_F/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_F/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_F/Cu_log2_manhattan_DMP_adj.png")

Cu, male
DMP_Cu_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Cu_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 10164
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 57164
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.911863
# Number of DMRs identified: 6
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Cu_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.2307306
# rm(DMP_Cu_M); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
5
|
83016999
|
83017184
|
0.0000000
|
185
|
0.0000000
|
0.0000001
|
4
|
|
3
|
46759437
|
46759698
|
0.0000000
|
261
|
0.0000000
|
0.0000021
|
7
|
|
1
|
108023248
|
108023482
|
0.0000001
|
234
|
0.0000001
|
0.0001015
|
5
|
|
12
|
54673866
|
54674009
|
0.0000036
|
143
|
0.0000053
|
0.0097873
|
4
|
|
6
|
32847761
|
32847830
|
0.0000643
|
69
|
0.0000772
|
0.3076772
|
5
|
|
7
|
94953876
|
94953956
|
0.0049862
|
80
|
0.0049862
|
1.0000000
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_M/Cu_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_M/Cu_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Cu_M/Cu_log2_manhattan_DMP_adj.png")

Hg
DMP_Hg_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Hg_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg')
# Unadjusted, N = 358
# Unadjusted, p<0.05: 38119
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 358
# Adjusted, p<0.05: 13462
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.7929906
# Number of DMRs identified: 2
# Global DNAm
pDatcordMetal_Hg = pDatcordMetal[!is.na(pDatcordMetal$Hg_log2),]
dim(pDatcordMetal_Hg)
# 358 164
ComBat.Betas.Metals_Hg = ComBat.Betas.Metals[,colnames(ComBat.Betas.Metals) %in% rownames(pDatcordMetal_Hg)]
ComBat.Betas.Metals_Hg = ComBat.Betas.Metals_Hg[,match(rownames(pDatcordMetal_Hg), colnames(ComBat.Betas.Metals_Hg))]
Z = as.matrix(ComBat.Betas.Metals_Hg)
y = pDatcordMetal_Hg$Hg_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_Hg)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.845803
# rm(DMP_Hg_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
8
|
143859668
|
143859990
|
0
|
322
|
0
|
0.00e+00
|
7
|
|
6
|
30039373
|
30039548
|
0
|
175
|
0
|
1.99e-05
|
12
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg/Hg_log2_manhattan_DMP_adj.png")

Hg, female
DMP_Hg_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Hg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_F')
# Unadjusted, N = 167
# Unadjusted, p<0.05: 11528
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 167
# Adjusted, p<0.05: 10298
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.7271097
# Number of DMRs identified: 1
# Global DNAm
pDatcordMetal_HgF = pDatcordMetal_Hg[pDatcordMetal_Hg$female_d == 1,]
dim(pDatcordMetal_HgF)
# 167 164
ComBat.Betas.Metals_HgF = ComBat.Betas.Metals[,colnames(ComBat.Betas.Metals) %in% rownames(pDatcordMetal_HgF)]
ComBat.Betas.Metals_HgF = ComBat.Betas.Metals_HgF[,match(rownames(pDatcordMetal_HgF), colnames(ComBat.Betas.Metals_HgF))]
Z = as.matrix(ComBat.Betas.Metals_HgF)
y = pDatcordMetal_HgF$Hg_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_HgF)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.9751191
# rm(DMP_Hg_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
6
|
31508105
|
31508137
|
3.95e-05
|
32
|
3.95e-05
|
0.3855435
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_F/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_F/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_F/Hg_log2_manhattan_DMP_adj.png")

Hg, male
DMP_Hg_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Hg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_M')
# Unadjusted, N = 191
# Unadjusted, p<0.05: 32177
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 191
# Adjusted, p<0.05: 12873
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.8093155
# Number of DMRs identified: 3
# Global DNAm
pDatcordMetal_HgM = pDatcordMetal_Hg[pDatcordMetal_Hg$female_d == 0,]
dim(pDatcordMetal_HgM)
# 191 164
ComBat.Betas.Metals_HgM = ComBat.Betas.Metals[,colnames(ComBat.Betas.Metals) %in% rownames(pDatcordMetal_HgM)]
ComBat.Betas.Metals_HgM = ComBat.Betas.Metals_HgM[,match(rownames(pDatcordMetal_HgM), colnames(ComBat.Betas.Metals_HgM))]
Z = as.matrix(ComBat.Betas.Metals_HgM)
y = pDatcordMetal_HgM$Hg_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_HgM)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.8570357
# rm(DMP_Hg_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
8
|
143859668
|
143859990
|
0
|
322
|
0
|
0e+00
|
7
|
|
6
|
31650785
|
31651362
|
0
|
577
|
0
|
2e-07
|
19
|
|
6
|
30039141
|
30039548
|
0
|
407
|
0
|
4e-07
|
15
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_M/Hg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_M/Hg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Hg_M/Hg_log2_manhattan_DMP_adj.png")

Mg
DMP_Mg_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Mg_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 20828
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 19876
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.067098
# Number of DMRs identified: 5
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Mg_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.469153
TestCDFs2(Z = Z, y = y, X = X)
# 0.3509856
# rm(DMP_Mg_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
20
|
57427169
|
57427973
|
0.0e+00
|
804
|
0.0e+00
|
0.0000000
|
24
|
|
6
|
30039174
|
30039548
|
0.0e+00
|
374
|
0.0e+00
|
0.0000000
|
13
|
|
6
|
32063990
|
32064258
|
0.0e+00
|
268
|
1.0e-07
|
0.0000461
|
12
|
|
1
|
2980037
|
2980163
|
2.5e-06
|
126
|
3.1e-06
|
0.0077603
|
2
|
|
11
|
368564
|
368712
|
6.6e-06
|
148
|
6.6e-06
|
0.0175234
|
7
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg/Mg_log2_manhattan_DMP_adj.png")

Mg, female
DMP_Mg_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Mg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 21465
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 15005
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.860424
# Number of DMRs identified: 5
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Mg_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.4382674
TestCDFs2(Z = Z, y = y, X = X)
# 0.5358737
# rm(DMP_Mg_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
17
|
48912264
|
48912621
|
0.00e+00
|
357
|
0.00e+00
|
0.0000000
|
9
|
|
20
|
57427442
|
57427762
|
0.00e+00
|
320
|
1.00e-07
|
0.0000298
|
13
|
|
2
|
121223739
|
121224009
|
1.00e-07
|
270
|
1.00e-07
|
0.0001158
|
6
|
|
14
|
105944941
|
105945022
|
1.60e-06
|
81
|
2.00e-06
|
0.0076408
|
2
|
|
19
|
45976119
|
45976195
|
4.01e-05
|
76
|
4.01e-05
|
0.1879917
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_F/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_F/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_F/Mg_log2_manhattan_DMP_adj.png")

Mg, male
DMP_Mg_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Mg_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 38543
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 40446
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.605054
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Mg_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.6190037
TestCDFs2(Z = Z, y = y, X = X)
# 0.3666586
# rm(DMP_Mg_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
19
|
57742111
|
57742423
|
0.0000000
|
312
|
0.0000000
|
0.0000000
|
7
|
|
22
|
22901829
|
22901880
|
0.0008779
|
51
|
0.0008779
|
0.9988789
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_M/Mg_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_M/Mg_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mg_M/Mg_log2_manhattan_DMP_adj.png")

Mn
DMP_Mn_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Mn_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 9732
# Unadjusted, FDR<0.05: 1
# Unadjusted, pBonf<0.05: 1
# Adjusted, N = 361
# Adjusted, p<0.05: 10167
# Adjusted, FDR<0.05: 1
# Adjusted, pBonf<0.05: 1
# Adjusted, lambda: 0.7325852
# Number of DMRs identified: 2
# Pathway analysis
GO_Mn = gometh(sig.cpg = DMP_Mn_cord[[3]]$cpg[DMP_Mn_cord[[3]]$adj.P.Val < 0.05], all.cpg = DMP_Mn_cord[[3]]$cpg, collection = "GO")
table(GO_Mn$P.DE < 0.05)
# FALSE TRUE
# 22583 27
table(GO_Mn$FDR < 0.05)
# FALSE
# 22610
KEGG_Mn = gometh(sig.cpg = DMP_Mn_cord[[3]]$cpg[DMP_Mn_cord[[3]]$adj.P.Val < 0.05], all.cpg = DMP_Mn_cord[[3]]$cpg, collection = "KEGG")
table(KEGG_Mn$P.DE < 0.05)
# FALSE
# 342
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Mn_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.9723614
# rm(DMP_Mn_cord); gc()
FDR-significant DMPs
|
|
logFC_CI
|
AveExpr
|
P.Value
|
adj.P.Val
|
adj.P.Val.bonf
|
chr
|
pos
|
gene
|
|
cg02042823
|
0.43 (0.31 ,0.55)
|
5.75
|
0
|
9.3e-06
|
0
|
chr16
|
6714429
|
A2BP1;A2BP1
|
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
6
|
32063725
|
32064161
|
0.0000000
|
436
|
0.0000000
|
0.0000038
|
13
|
|
7
|
1250125
|
1250182
|
0.0017739
|
57
|
0.0017739
|
0.9999954
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn/Mn_log2_manhattan_DMP_adj.png")

Mn, female
DMP_Mn_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Mn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 26444
# Unadjusted, FDR<0.05: 3
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 13233
# Adjusted, FDR<0.05: 9
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.8939725
# Number of DMRs identified: 7
GO_Mn_F = gometh(sig.cpg = DMP_Mn_F_cord[[3]]$cpg[DMP_Mn_F_cord[[3]]$adj.P.Val < 0.05], all.cpg = DMP_Mn_F_cord[[3]]$cpg, collection = "GO")
table(GO_Mn_F$P.DE < 0.05)
# FALSE TRUE
# 22481 129
table(GO_Mn_F$FDR < 0.05)
# FALSE
# 22610
KEGG_Mn_F = gometh(sig.cpg = DMP_Mn_F_cord[[3]]$cpg[DMP_Mn_F_cord[[3]]$adj.P.Val < 0.05], all.cpg = DMP_Mn_cord_F[[3]]$cpg, collection = "KEGG")
table(KEGG_Mn_F$P.DE < 0.05)
# FALSE TRUE
# 334 8
table(KEGG_Mn_F$FDR < 0.05)
# FALSE
# 342
write.csv(KEGG_Mn_F, '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_F/KEGG.csv')
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Mn_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.3499748
TestCDFs2(Z = Z, y = y, X = X)
# 0.7004179
# rm(DMP_Mn_F_cord); gc()
FDR-significant DMPs
|
|
logFC_CI
|
AveExpr
|
P.Value
|
adj.P.Val
|
adj.P.Val.bonf
|
chr
|
pos
|
gene
|
|
cg00954161
|
0.42 (0.27 ,0.57)
|
5.99
|
2e-07
|
0.0341269
|
0.0801
|
chr1
|
3696925
|
LRRC47
|
|
cg01744822
|
-0.22 (-0.31 ,-0.14)
|
-4.36
|
9e-07
|
0.0442988
|
0.3421
|
chr16
|
73100510
|
|
|
cg08904630
|
0.21 (0.13 ,0.29)
|
5.33
|
9e-07
|
0.0442988
|
0.3514
|
chr10
|
71490427
|
|
|
cg11161853
|
-0.14 (-0.19 ,-0.08)
|
-5.29
|
9e-07
|
0.0442988
|
0.3738
|
chr3
|
67705044
|
SUCLG2
|
|
cg15712310
|
-0.19 (-0.26 ,-0.12)
|
-1.62
|
2e-07
|
0.0341269
|
0.0717
|
chr16
|
73100790
|
|
|
cg19908812
|
-0.17 (-0.24 ,-0.1)
|
-6.02
|
9e-07
|
0.0442988
|
0.3659
|
chr4
|
164253006
|
NPY1R
|
|
cg22799518
|
0.52 (0.33 ,0.71)
|
6.34
|
3e-07
|
0.0341269
|
0.1365
|
chr12
|
56988862
|
RBMS2
|
|
cg23903787
|
0.34 (0.22 ,0.47)
|
3.02
|
3e-07
|
0.0341269
|
0.1141
|
chr4
|
3527371
|
LRPAP1
|
|
cg26462130
|
0.39 (0.24 ,0.53)
|
6.11
|
1e-06
|
0.0442988
|
0.3987
|
chr7
|
2052961
|
MAD1L1;MAD1L1;MAD1L1
|
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
16
|
73100425
|
73100790
|
0e+00
|
365
|
0e+00
|
0.0000000
|
3
|
|
3
|
148804271
|
148804556
|
0e+00
|
285
|
0e+00
|
0.0000004
|
8
|
|
3
|
67704889
|
67705285
|
0e+00
|
396
|
0e+00
|
0.0000005
|
6
|
|
6
|
161561030
|
161561121
|
0e+00
|
91
|
0e+00
|
0.0000071
|
3
|
|
7
|
3019158
|
3019382
|
0e+00
|
224
|
0e+00
|
0.0000054
|
4
|
|
7
|
27170716
|
27171051
|
0e+00
|
335
|
0e+00
|
0.0000047
|
9
|
|
13
|
97646638
|
97646765
|
5e-07
|
127
|
5e-07
|
0.0016533
|
4
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_F/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_F/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_F/Mn_log2_manhattan_DMP_adj.png")

Mn, male
DMP_Mn_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Mn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 9543
# Unadjusted, FDR<0.05: 2
# Unadjusted, pBonf<0.05: 2
# Adjusted, N = 192
# Adjusted, p<0.05: 12799
# Adjusted, FDR<0.05: 2
# Adjusted, pBonf<0.05: 2
# Adjusted, lambda: 0.8388281
# Number of DMRs identified: 4
GO_Mn_M = gometh(sig.cpg = DMP_Mn_M_cord[[3]]$cpg[DMP_Mn_M_cord[[3]]$adj.P.Val < 0.05], all.cpg = DMP_Mn_M_cord[[3]]$cpg, collection = "GO")
table(GO_Mn_M$P.DE < 0.05)
# FALSE TRUE
# 22586 24
table(GO_Mn_M$FDR < 0.05)
# FALSE
# 22610
KEGG_Mn_M = gometh(sig.cpg = DMP_Mn_M_cord[[3]]$cpg[DMP_Mn_M_cord[[3]]$adj.P.Val < 0.05], all.cpg = DMP_Mn_M_cord[[3]]$cpg, collection = "KEGG")
table(KEGG_Mn_M$P.DE < 0.05)
# FALSE
# 342
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Mn_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.3561523
TestCDFs2(Z = Z, y = y, X = X)
# 0.5219932
# rm(DMP_Mn_M_cord); gc()
FDR-significant DMPs
|
|
logFC_CI
|
AveExpr
|
P.Value
|
adj.P.Val
|
adj.P.Val.bonf
|
chr
|
pos
|
gene
|
|
cg02042823
|
0.51 (0.36 ,0.66)
|
5.71
|
0
|
0.0001241
|
0.0001
|
chr16
|
6714429
|
A2BP1;A2BP1
|
|
cg03763518
|
-0.29 (-0.39 ,-0.19)
|
-3.51
|
0
|
0.0091811
|
0.0184
|
chr1
|
150245044
|
C1orf54
|
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
20
|
36148603
|
36149271
|
0e+00
|
668
|
0e+00
|
0.0000000
|
31
|
|
7
|
1250087
|
1250273
|
0e+00
|
186
|
0e+00
|
0.0000000
|
7
|
|
15
|
99789621
|
99789855
|
0e+00
|
234
|
0e+00
|
0.0000030
|
5
|
|
1
|
75198817
|
75199117
|
1e-07
|
300
|
1e-07
|
0.0001093
|
6
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_M/Mn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_M/Mn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Mn_M/Mn_log2_manhattan_DMP_adj.png")

Pb
DMP_Pb_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Pb_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 25856
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 14691
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.8763417
# Number of identified DMR: 0
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Pb_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.2242514
TestCDFs2(Z = Z, y = y, X = X)
# 0.9723614
# rm(DMP_Pb_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb/Pb_log2_manhattan_DMP_adj.png")

Pb, female
DMP_Pb_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Pb_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 16597
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 20414
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.132739
# Number of identified DMR: 0
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Pb_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.07160096
TestCDFs2(Z = Z, y = y, X = X)
# 0.2744584
# rm(DMP_Pb_F_cord); gc()
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_F/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_F/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_F/Pb_log2_manhattan_DMP_adj.png")

Pb, male
DMP_Pb_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Pb_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 19998
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 13522
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.8591965
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Pb_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 1
TestCDFs2(Z = Z, y = y, X = X)
# 0.9140094
# rm(DMP_Pb_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
14
|
100203941
|
100204258
|
0
|
317
|
0
|
1.9e-06
|
6
|
|
3
|
122640777
|
122641144
|
0
|
367
|
0
|
6.5e-06
|
4
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_M/Pb_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_M/Pb_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Pb_M/Pb_log2_manhattan_DMP_adj.png")

Se
DMP_Se_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Se_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 23447
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 15897
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.8643957
# Number of DMRs identified: 2
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Se_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.1214307
TestCDFs2(Z = Z, y = y, X = X)
# 0.2808225
# rm(DMP_Se_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
8
|
144635259
|
144635610
|
0
|
351
|
0
|
7.90e-06
|
9
|
|
4
|
74847645
|
74847829
|
0
|
184
|
0
|
4.18e-05
|
7
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se/Se_log2_manhattan_DMP_adj.png")

Se, female
DMP_Se_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Se_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_F')
# # Unadjusted, N = 169
# Unadjusted, p<0.05: 11702
# Unadjusted, FDR<0.05: 1
# Unadjusted, pBonf<0.05: 1
# Adjusted, N = 169
# Adjusted, p<0.05: 10751
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 0.717438
# Number of DMRs identified: 4
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Se_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.6522482
TestCDFs2(Z = Z, y = y, X = X)
# 0.876843
# rm(DMP_Se_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
8
|
144635259
|
144636113
|
0.0000000
|
854
|
0.0000000
|
0.0000000
|
12
|
|
15
|
75019069
|
75019376
|
0.0000000
|
307
|
0.0000000
|
0.0000318
|
10
|
|
19
|
1510493
|
1510692
|
0.0000000
|
199
|
0.0000000
|
0.0000645
|
4
|
|
18
|
23713837
|
23714009
|
0.0002329
|
172
|
0.0002329
|
0.4138549
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_F/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_F/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_F/Se_log2_manhattan_DMP_adj.png")

Se, male
DMP_Se_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Se_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 28127
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 23097
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.035939
# Number of DMRs identified: 1
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Se_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.04829198
TestCDFs2(Z = Z, y = y, X = X)
# 0.1484135
# rm(DMP_Se_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
19
|
57742254
|
57742423
|
0
|
169
|
0
|
2.7e-06
|
6
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_M/Se_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_M/Se_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Se_M/Se_log2_manhattan_DMP_adj.png")

Zn
DMP_Zn_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal, var = 'Zn_log2', covar = c('female_d', 'race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn')
# Unadjusted, N = 361
# Unadjusted, p<0.05: 25089
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 361
# Adjusted, p<0.05: 37705
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.490786
# Number of DMRs identified: 6
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals)
y = pDatcordMetal$Zn_log2
X = model.matrix(~ female_d + race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.6606383
TestCDFs2(Z = Z, y = y, X = X)
# 0.2234394
# rm(DMP_Zn); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
3
|
48632483
|
48632783
|
0.00e+00
|
300
|
0.00e+00
|
0.0000004
|
8
|
|
17
|
79503641
|
79503877
|
0.00e+00
|
236
|
0.00e+00
|
0.0000010
|
4
|
|
12
|
1973871
|
1974168
|
0.00e+00
|
297
|
0.00e+00
|
0.0000053
|
3
|
|
11
|
92702372
|
92702912
|
0.00e+00
|
540
|
0.00e+00
|
0.0000053
|
8
|
|
20
|
25129506
|
25129562
|
5.00e-06
|
56
|
6.00e-06
|
0.0348380
|
5
|
|
6
|
32165175
|
32165200
|
7.09e-05
|
25
|
7.09e-05
|
0.6735463
|
3
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn/Zn_log2_manhattan_DMP_adj.png")

Zn, female
DMP_Zn_F_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_F, var = 'Zn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_F')
# Unadjusted, N = 169
# Unadjusted, p<0.05: 35062
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 169
# Adjusted, p<0.05: 17286
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.062488
# Number of DMRs identified: 1
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_F)
y = pDatcordMetal_F$Zn_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_F)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.5894776
TestCDFs2(Z = Z, y = y, X = X)
# 0.2311608
# rm(DMP_Zn_F_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
3
|
138763669
|
138763910
|
0
|
241
|
0
|
0
|
5
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_F/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_F/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_F/Zn_log2_manhattan_DMP_adj.png")

Zn, male
DMP_Zn_M_cord = run_EWAS(DNAm = ComBat.Mvalues.Metals, pheno = pDatcordMetal_M, var = 'Zn_log2', covar = c('race_child2', 'gestage_wks_deliv_d', 'age_mom_enroll_d', 'bmi_mom_prepreg_d', 'coll_grad', 'nullip', 'gt70k', 'smk_preg', 'Bcell_GS_cb', 'CD4T_GS_cb', 'CD8T_GS_cb', 'Gran_GS_cb', 'Mono_GS_cb', 'NK_GS_cb', 'nRBC_GS_cb'), anno = anno, path = '/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_M')
# Unadjusted, N = 192
# Unadjusted, p<0.05: 10405
# Unadjusted, FDR<0.05: 0
# Unadjusted, pBonf<0.05: 0
# Adjusted, N = 192
# Adjusted, p<0.05: 22001
# Adjusted, FDR<0.05: 0
# Adjusted, pBonf<0.05: 0
# Adjusted, lambda: 1.099038
# Number of DMRs identified: 4
# Global DNAm
Z = as.matrix(ComBat.Betas.Metals_M)
y = pDatcordMetal_M$Zn_log2
X = model.matrix(~ race_child2 + gestage_wks_deliv_d + age_mom_enroll_d + bmi_mom_prepreg_d + coll_grad + nullip + gt70k + smk_preg + Bcell_GS_cb + CD4T_GS_cb + CD8T_GS_cb + Gran_GS_cb + Mono_GS_cb + NK_GS_cb + nRBC_GS_cb, data = pDatcordMetal_M)[,-1]
TestDensities2(Z = Z, y = y, X = X)
# 0.8342179
TestCDFs2(Z = Z, y = y, X = X)
# 0.7287762
# rm(DMP_Zn_M_cord); gc()
DMRs
|
chr
|
start
|
end
|
p
|
length
|
fdr
|
sidak
|
nprobe
|
|
13
|
110319561
|
110319607
|
0.0000000
|
46
|
0.0000000
|
4.29e-05
|
3
|
|
5
|
112824496
|
112824765
|
0.0000000
|
269
|
0.0000000
|
9.90e-06
|
6
|
|
1
|
1361654
|
1361729
|
0.0000000
|
75
|
0.0000000
|
4.20e-05
|
3
|
|
6
|
31651019
|
31651029
|
0.0077377
|
10
|
0.0077377
|
1.00e+00
|
2
|
knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_M/Zn_log2_QQ_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_M/Zn_log2_volcano_DMP_adj.png")

knitr::include_graphics("/Users/annebozack/Documents/Cardenas/viva_DNAm_metals_local/CordBlood/Zn_M/Zn_log2_manhattan_DMP_adj.png")
